A target-group-change couple with mass defect filtering strategy to identify the metabolites of "Dogel ebs" in rats plasma, urine and bile.

"Dogel ebs" was known as Sophora flavescens Ait., a classical traditional Chinese Mongolian herbal medicine, which had the effects on damp-heat dysentery, scrofula, and syndrome of accumulated dampness toxicity. Although the chemical constituents have been clarified by our previous studies, the metabolic transformation of "Dogel ebs" in vivo was still unclear. To explore the mechanism of "Dogel ebs," the metabolites in plasma, bile, and urine samples were investigated. A fast positive and negative ion switching technology was used for the simultaneous determination of flavonoids and alkaloids in "Dogel ebs" in a single run. And a target-group-change coupled with mass defect filtering strategy was utilized to analyze the collected data. 89 parent compounds and 82 metabolites were characterized by high-performance liquid chromatography with quadrupole exactive Orbitrap mass spectrometry. Both phase I and phase II metabolites were observed and the metabolic pathways involved in oxidation, demethylation, acetylation, and glucuronidation. 69 metabolites of "Dogel ebs," including three hydroxyls bonding xanthohumol, formononetin-7-O-glucuronide, 2'-hydroxyl-isoxanthohumol decarboxylation metabolite, oxysophocarpine dehydrogen, 9α-hydroxysophoramine-O-glucuronide, etc. were reported for the first time.

Cytotoxic activities of flavonoids from a traditional Mongolian medicinal herb Clematis aethusifolia Turcz.

In the course of our search for antitumour constituents from the traditional Mongolian medicinal herb Clematis aethusifolia Turcz., 11 flavonoids were isolated for the first time from the dried aerial parts of the plant by flash C18 column chromatography, Sephadex LH-20 and reversed phase preparative HPLC. The planar structures of these flavonoids were established based on 1D and 2D NMR and high-resolution mass spectrometry. Compounds 1, 2, 4 and 5 showed moderate cytotoxicity against a panel of five human solid tumour cell lines, including A-375, a human melanoma cell line; SK-OV-3, a human ovarian cancer cell line; A549, a human lung cancer cell line; HCT-15, a human colorectal adenocarcinoma cell line; and SH-SY5Y, a human neuroblastoma cell line (with IC50 values of 20-70 µM). The obtained cytotoxic apigenin and its derivatives may be useful as standard compounds for the quality control of the crude drug and its preparations.

[Chemical Constituents from A Taditional Mongolian Medicine Clematis aethusifolia].

Objective: To investigate the chemical constituents of Clematis aethusifolia,a traditional Mongolian medicine for resolving hard lump. Methods: Bioactive guided isolation and purification of Clematis aethusifolia was performed by normal and reverse phase column chromatography, Sephadex LH-20 and preparation HPLC. The structures were identified by 1D,2D-NMR and MS spectral analysis and comparison with literature data. Cytotoxicity of compounds were determined by CCK-8 cell staining method for detecting growth inhibition to five kinds of human solid tumor cell lines. Results: Eight compounds were isolated and identified as vanillicacid( 1),protocatechuic acid( 2),( +)-pinoresinol diglucoside( 3),( +)-pinoresinol-4'-O-ß-D-glucopyranoside( 4),( +)-syringaresinol-4'-O-ß-Dglucopyranoside( 5),7,9,9'-trihydroxy-3,3'-dimethoxy-8-O-4'-neolignan-4-O-ß-D-glucopyranoside( 6),butyl-ß-D-fructopyranoside( 7),butyl-ß-D-fructofuranoside( 8). Compounds 2,8 showed strong cytotoxic activity. Conclusion: All the compounds are isolated from this plant for the first time, Results: Eight compounds were isolated and identified as vanillicacid( 1), protocatechuic acid( 2),( +)-pinoresinol diglucoside( 3),( +)-pinoresinol-4'-O-ß-D-glucopyranoside( 4),( +)-syringaresinol-4'-O-ß-Dglucopyranoside( 5),7,9,9'-trihydroxy-3,3'-dimethoxy-8-O-4'-neolignan-4-O-ß-D-glucopyranoside( 6),butyl-ß-D-fructopyranoside( 7),butyl-ß-D-fructofuranoside( 8). Compounds 2,8 showed strong cytotoxic activity. compounds 3,6 ~ 8 are isolated from Clematis genus for the first time, compounds 6 and 8 are isolated from Ranunculaceae family for the first time. Compounds 2,8 may be the effective components in Clematis aethusifolia.

[Study on the Flavonoids and Biological Activity of Rubus sachalinensis].

Objective: To study the chemical constituents and biological activity of Rubus sachalinensis. Methods: The compounds in the ethyl acetate and n-butanol fraction were isolated and purified by macroporous resin,Sephadex LH-20 column chromatography,and reverse-phase preparative HPLC. The structures were identified by various spectroscopic data such as 1D,2D-NMR,HRMS. Antioxidant,anti-inflammatory and cytotoxicity of the compounds were determined by FRAP,Griess and MTT methods. Results: Eight compounds were isolated from the ethyl acetate and n-butanol extract of Rubus sachalinensis,and identified as kaempferol-3-O-ß-D-butyl glucuronate( 1),quercetin-3-O-ß-D-butyl glucuronate( 2),quercetin-3-O-ß-D-glucopyranoside( 3),cis-tiliroside( 4),tiliroside( 5),quercetin-3-O-ß-D-ethyl glucuronate( 6),quercetin( 7) and kaempferol( 8). Activity assay showed that the compounds 1 ~ 8 had different levels of antioxidant activity,all the compounds showed cytotoxicities of IC50 greater than 200 µmol / L. Conclusion: Flavonoids are the main antioxidant consitituents of Rubus sachalinensis and have a good anti-inflammatory activity. All the compounds are isolated from this plant for the first time,compounds 1,2,6 are obtained from the this genus for the first time.

Marine-derived Aspergillus species as a source of bioactive secondary metabolites.

This report reviews biologically active secondary metabolites from marine-derived members of the fungal genus Aspergillus. Pharmacological activities and biological roles of the secondary metabolites from marine-derived Aspergillus spp. were addressed in respect of pharmaceutical potential.

Bicyclic alpha,omega-dicarboxylic acid derivatives from a colonial tunicate of the family Polyclinidae.

In the course of our search for bioactive metabolites from a colonial tunicate of the family Polyclinidae, six new (1-6) cyclic fatty acid derivatives were isolated. Their planar structures were established on the basis of NMR and MS spectroscopic analyses. The relative configuration was determined by NOESY experiment. Compounds 1-6 represent a fused bicyclic skeleton possibly derived from alpha,omega-dicarboxylic acids such as eicosanedioic acid or docosanedioic acid via a Diels-Alder type of cyclization. Compounds 1-4 and 6 showed mild cytotoxicity against a panel of five human solid tumor cell lines.

Anti-inflammatory sesquiterpenoids from a sponge-derived Fungus Acremonium sp.

In the course of our search for bioactive metabolites from a sponge-derived fungus Acremonium sp., new sesquiterpenoids (1-4) were isolated along with known derivatives by bioactivity-guided fractionation. The unique cyclic skeleton of compounds 2 and 3 is unprecedented. The absolute configurations were determined by modified Mosher's method and CD spectroscopy, along with comparison of (1)H and (13)C NMR spectroscopic data and specific optical rotation values with those reported. The anti-inflammatory activity of the isolated compounds (1, 5, 7-13) was evaluated by measuring their inhibitory effects on the production of pro-inflammatory mediators (NO, IL-6, and TNF-alpha) in RAW 264.7 murine macrophage cells. Among the compounds tested, compounds 7 and 9 significantly inhibited the production of NO and TNF-alpha at the concentration of 100 microM, while compounds 11 and 12 showed selective inhibition of NO production at the same concentration.

New cerebrosides from a marine sponge Haliclona (Reniera) sp.

A chemical investigation of the MeOH extract of a marine sponge Haliclona (Reniera) sp., collected off the coast of Ulleung Island, Korea, led to the isolation of thirteen new cerebrosides (1--3, 5--14), along with a known analogue (4). Their structures were elucidated on the basis of 1D and 2D NMR spectroscopy, MS spectrometry, and chemical method. The major new features of these glucocerebrosides are C15 and C19 acyl chains, long (C24-C28) acyl chains, or the S-configuration of the acyl chains. It is noteworthy that both R- and S-configurations of the acyl chains were observed in the same specimen.

New jasmonate analogues as potential anti-inflammatory agents.

In an effort to develop new anti-inflammatory agents, methyl jasmonate analogues (2-20) were synthesized and evaluated for their inhibitory effects on the production of pro-inflammatory mediators (NO, IL-6, and TNF-alpha) in lipopolysaccharide (LPS)-activated RAW264.7 murine macrophage cells. The introduction of an enone functionality to the structure of a plant hormone (1) rendered the product (2) a significant anti-inflammatory activity. Analogues further derived from 2 (7, 9, 13, and 15) exhibited even more enhanced activity, and these compounds were much more potent than natural anti-inflammatory prostaglandins (PGA(1), PGA(2), and 15-deoxy-Delta(12,14)-PGJ(2)). Among them, compounds 9 and 15 showed the highest potency, while compounds 7 and 13 would be more desirable with respect to safety. This is the first study demonstrating the anti-inflammatory potential of jasmonate derivatives, and the present results suggest that alpha-haloenone jasmonates (7, 9, 13, and 15) may serve as potential anti-inflammatory leads.

Bisindole alkaloids of the topsentin and hamacanthin classes from a marine sponge Spongosorites sp.

Seven new (1 and 3-8) and seven known (2 and 9-14) bisindole alkaloids of the topsentin and hamacanthin classes were isolated from the MeOH extract of a marine sponge Spongosorites sp. by bioactivity-guided fractionation. The structure of compound 7 is a revision from our previous report. The planar structures were established on the basis of NMR and MS spectroscopic analyses. Configurations of these compounds were defined by NMR spectroscopy and optical rotation. It is noteworthy that both R and S isomers were isolated for the hamacanthins (1-4, 9, 10, 15, and 16), while a single stereoisomer was isolated for dihydrohamacanthins (5, 11-14, 17, and 18). Compounds 1-4, 6, and 8-14 showed marginal cytotoxicity against five human solid tumor cell lines, and compound 2 showed weak antibacterial activity against clinically isolated methicillin-resistant strains.

Monoindole alkaloids from a marine sponge Spongosorites sp.

Seven (1-7) monoindole derivatives were isolated from the MeOH extract of a marine sponge Spongosorites sp. by bioactivity-guided fractionation. The planar structures were established on the basis of NMR and MS spectroscopic analyses. Compounds 1-5 are unique indole pyruvic acid derivatives. Compounds 1-2 and 4-6 are isolated for the first time from a natural source although they were previously reported as synthetic intermediates. Compound 3 was defined as a new compound. Co-occurring bisindoles such as hamacanthins and topsentins might be biosynthesized by condensation of two units of these compounds. The compounds were tested for cytotoxicity against a panel of five human solid tumor cell lines, and compound 7 displayed weak activity.

Cytotoxic bisindole alkaloids from a marine sponge Spongosorites sp.

Three new bisindole alkaloids of the hamacanthin class (1-3) and one new bisindole alkaloid of the topsentin class (6) were isolated along with known bisindole alkaloids (4, 5, 7-11) from the MeOH extract of a marine sponge Spongosorites sp. by bioactivity-guided fractionation. The planar structures were established on the basis of NMR, MS, and IR spectroscopic analyses. Configurations of compounds 1-4 were derived from 1H NMR data and optical rotation. Compounds 1, 4, 5, and 11 showed moderate to significant cytotoxicity against five human tumor cell lines, and compounds 1-5 showed weak antibacterial activity against clinically isolated methicillin-resistant strains.